Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health. Therefore, this study examined patients who underwent breast cancer surgery, analyzed hospitalization costs and structure, and explored the impact of China Healthcare Security Diagnosis Related Groups (CHS-DRG) management on patient costs. It aimed to provide medical institutions with ways to reduce costs, optimize cost structures, reduce patient burden, and improve service efficiency. AIM: To study the CHS-DRG payment system's impact on breast cancer surgery costs. METHODS: Using the CHS-DRG (version 1.1) grouping criteria, 4073 patients, who underwent the radical resection of breast malignant tumors from January to December 2023, were included in the JA29 group; 1028 patients were part of the CHS-DRG payment system, unlike the rest. Through an independent sample t-test, the length of hospital stay as well as total hospitalization, medicine and consumables, medical, nursing, medical technology, and management expenses were compared. Pearson's correlation coefficient was used to test the cost correlation. RESULTS: In terms of hospitalization expenses, patients in the CHS-DRG payment group had lower medical, nursing, and management expenses than those in the diagnosis-related group (DRG) non-payment group. For patients in the DRG payment group, the factors affecting the total hospitalization cost, in descending order of relevance, were medicine and consumable costs, consumable costs, medicine costs, medical costs, medical technology costs, management costs, nursing costs, and length of hospital stay. For patients in the DRG non-payment group, the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses, consumable expenses, medical technology expenses, the cost of medicines, medical expenses, nursing expenses, length of hospital stay, and management expenses. CONCLUSION: The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs, medical consumable costs, and the length of hospital stay while ensuring medical safety.

Access to essential and innovative anti-cancer medicines: a longitudinal study in Nanjing, China.

PURPOSE: To evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu. METHODS: A longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated. RESULTS: The availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents. CONCLUSIONS: There were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.

Silencing CK19 regulates ferroptosis by affecting the expression of GPX4 and ACSL4 in oral squamous cell carcinoma in vivo and in vitro.

To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.

[Effect of Hei Xiaoyaosan regulating p38MAPK/Beclin-1/Bcl-2 pathway on autophagy level in Alzheimer's disease model rats].

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).

Zinc proteinate with moderate chelation strength enhances zinc absorption by up-regulating the expression of zinc and amino acid transporters in primary cultured duodenal epithelial cells of broiler embryos.

Recent study showed that zinc (Zn) and amino acid transporters may be involved in enhancing Zn absorption from Zn proteinate with moderate chelation strength (Zn-Prot M) in the duodenum of broilers. However, the specific mechanisms by which Zn-Prot M promotes the above Zn absorption are unknown. Therefore, in this study, three experiments were conducted to investigate specific and direct effects of Zn-Prot M and Zn sulfate (ZnS) on Zn absorption and expression of related transporters in primary duodenal epithelial cells of broiler embryos so as to preliminarily address possible mechanisms. In experiment 1, cells were treated with 100 µmol Zn/L as ZnS or Zn-Prot M for 20, 40, 60, 80, 100 or 120 min. Experiment 2 consisted of 3 sub-experiments. In experiment 2A, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 100 or 200 µmol Zn/L as ZnS or Zn-Prot M for 60 min; in experiment 2B, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 200 µmol Zn/L of as the ZnS or Zn-Prot M for 120 min; in experiment 2C, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 or 800 µmol Zn/L as ZnS or Zn-Prot M for 120 min. In experiment 3, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 µmol Zn/L as ZnS or Zn-Prot M for 120 min. The results of experiment 1 indicated that the minimum incubation time for saturable Zn absorption was determined to be 50.83 min using the best fit line. The results in experiment 2 demonstrated that a Zn concentration of 400 µmol/L and an incubation time of 120 min were suitable to increase the absorption of Zn from Zn-Prot M compared to ZnS. In experiment 3, Zn absorption across cell monolayers was significantly increased by Zn addition (P < 0.05), and was significantly greater with Zn-Prot M than with ZnS (P < 0.05). Compared to the control, Zn addition significantly decreased Zn transporter 10 and peptide-transporter 1 mRNA expression levels and increased y+L-type amino transporter 2 (y+LAT2) protein abundance (P < 0.05). Moreover, protein expression levels of zrt/irt-like protein 3 (ZIP3), ZIP5 and y+LAT2 were significantly greater for Zn-Prot M than for ZnS (P < 0.05). These findings suggest that Zn-Prot M promote Zn absorption by increasing ZIP3, ZIP5 and y+LAT2 protein expression levels in primary duodenal epithelial cells.

Emerging approaches of utilizing trees to produce advanced structural and functional materials.

The global number of trees is approximately 3 trillion, covering 31% of the land area. Trees are considered a cheap, abundant, renewable, and environmentally friendly feedstock for producing advanced structural and functional materials toward a widespread application in sustainable energy and environment. In this highlight, we reveal the structure and composition of wood, leaves, and tree extracts, and then highlight the strategies to control their hierarchical structures and properties. Moreover, we provide an up-to-date overview of their emerging applications in sustainable buildings, ionic nanofluidics, batteries, capacitors, solar cells, environmental remediation, biodegradable packaging, and nanomaterial synthesis. Finally, we outline the challenges and opportunities in valorizing trees for creating a sustainable future.

Light-induced ß-hydroxy sulfone synthesis in DNA-encoded libraries.

We here describe a visible-light photooxidation of sulfinate salts with common alkenes to yield ß-hydroxy sulfones on DNA. This process demonstrates a broad substrate compatibility and achieves conversion rates ranging from moderate to excellent. Most importantly, it presents a straightforward, efficient, and metal-free approach for synthesizing Csp3-rich DNA-encoded libraries.

Green space exposure and Chinese residents' physical activity participation: empirical evidence from a health geography perspective.

Background: With continuous efforts made to promote the strategic goals of carbon neutrality and carbon peak, it is crucial to meet the growing and diversified needs of the public for fitness by practicing the concept of green development and promote the combination of national fitness and ecological civilization. Methods: To achieve this purpose, an OLS regression model was applied to estimate the role of green space exposure in Chinese residents' participation in physical activity and its underlying mechanisms, using the microdata from the China General Social Survey (CGSS) data and the Provincial Vegetation Cover Index (NDVI) matched macrostatistical data. Results: The empirical results show that green space exposure significantly increases the probability of residents' physical activity participation, and creating a green environment is conducive to creating a favorable physical activity environment for residents. Also, the core conclusions still hold after the year-by-year regression test is passed and the endogeneity problem is addressed. As revealed by mechanistic studies, green space exposure has indirect effects on the physical activity participation of residents through the independent mediating roles of reducing carbon emissions and promoting social interaction. According to heterogeneity results, males, those in marriage, and urban dweller groups are more inclined to perform physical activity in green spaces. Conclusion: The results show that the exposure of green space can help increase the probability of residents' participation in physical exercise, and can that it achieved through two channels: reducing carbon emissions and enhancing social interaction. It is necessary to further strengthen the protection of the ecological lifestyle, give full play to the advantages of greenness and low-carbon, and create favorable conditions for the green development of a new model of national fitness.

Comparative mitogenome research revealed the phylogenetics and evolution of the superfamily Tenebrionoidea (Coleoptera: Polyphage).

Despite the worldwide distribution and rich diversity of the superfamily Tenebrionoidea, the knowledge of the mitochondrial genomes (mtgenome) characteristics of the superfamily is still very limited, and its phylogenetics and evolution remain unresolved. In the present study, we newly sequenced mtgenomes from 19 species belonging to Tenebrionoidea, and a total of 90 mitochondrial genomes from 16 families of Tenebrionoidea were used for phylogenetic analysis. There exist 37 genes for all 82 species of complete mtgenomes of 16 families investigated, and their characteristics are identical as reported mtgenomes of other Tenebrionoids. The Ka/Ks analysis suggests that all 13 PCGs have undergone a strong purifying selection. The phylogenetic analysis suggests the monophyly of Mordellidae, Meloidae, Oedemeridae, Pyrochroidae, Salpingidae, Scraptiidae, Lagriidae, and Tenebrionidae, and the Mordellidae is close to the Ripiphoridae. The "Tenebrionidae clade" and "Meloidae clade" are monophyletic, and both of them are sister groups. In the "Meloidae clade," Meloidae is close to Anthicidae. In the "Tenebrionidae clade," the family Lagriidae and Tenebrionidae are sister groups. The divergence time analysis suggests that Tenebrionoidea originated in the late Jurassic, Meloidae Mordellidae, Lagriidae, and Tenebrionidae in the Cretaceous, Oedemeridae in Paleogene. The work lays a base for the study of mtgenome, phylogenetics, and evolution of the superfamily Tenebrionoidea.

Nomogram for predicting 5-year metabolic dysfunction-associated steatotic liver disease risk: retrospective cohort study.

Objective: To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using eight variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides, and high-density lipoprotein), we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% CI: 0.779-0.811) in the training set and 0.785 (95% CI: 0.760-0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%. Conclusion: We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.

Two Undescribed Coumarins from Notopterygium incisum with Anti-inflammatory Activity.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

Benzodioxane Carboxamide Derivatives As Novel Monoamine Oxidase B Inhibitors with Antineuroinflammatory Activity.

In this study, a series of N-phenyl-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide derivatives were designed, synthesized, and evaluated for their inhibitory activities against human MAO-B (hMAO-B). The structure-activity relationship (SAR) was investigated and summarized. Compound 1l (N-(3,4-dichlorophenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide) showed the most potent inhibitory activity with an IC50 value of 0.0083 µM and the selectivity index (IC50 (hMAO-A)/IC50 (hMAO-B)) was >4819. Kinetics and reversibility studies confirmed that compound 1l acted as a competitive and reversible inhibitor of hMAO-B. Molecular docking studies revealed the enzyme-inhibitor interactions, and the rationale was provided. Additionally, compound 1l could effectively inhibit the release of NO, TNF-α, and IL-1ß in both LPS- and Aß1-42-stimulated BV2 cells and attenuate the cytotoxicity induced by Aß1-42. Since compound 1l exhibited low neurotoxicity, we believe that the hit compound with dual activities of inhibiting MAO-B and antineuroinflammation could be further investigated as a novel potential lead for future studies in vivo.

Effects of the "AI-TA" Mobile App With Intelligent Design on Psychological and Related Symptoms of Young Survivors of Breast Cancer: Randomized Controlled Trial.

BACKGROUND: Young women often face substantial psychological challenges in the initial years following cancer diagnosis, leading to a comparatively lower quality of life than older survivors. While mobile apps have emerged as potential interventions, their effectiveness remains inconclusive due to the diversity in intervention types and variation in follow-up periods. Furthermore, there is a particular dearth of evidence regarding the efficacy of these apps' intelligent features in addressing psychological distress with these apps. OBJECTIVE: This study aims to evaluate the effectiveness of a mobile app with intelligent design called "AI-TA" on cancer-related psychological health and ongoing symptoms with a randomized controlled design. METHODS: Women aged 18 to 45 years diagnosed with breast cancer were randomly assigned to the intervention or control group. The intervention was AI-TA, which included 2-way web-based follow-up every 2 weeks. Both intention-to-treat (ITT) and per-protocol (PP) analyses employed repeated measurement analysis of variance. The participants' background features, primary outcomes (psychological distress and frequency, self-efficacy, and social support), and secondary outcomes (quality of life) were measured using multiple instruments at 3 time points (baseline, 1-month intervention, and 3-month intervention). RESULTS: A total of 124 participants were randomly allocated to the control group (n=62, 50%) or intervention group (n=62, 50%). In total, 92.7% (115/124) of the participants completed the intervention. Significant improvements in psychological symptoms (Memorial Symptom Assessment Scale-Short Form) were observed in the ITT group from baseline to 1-month intervention relative to the control group (ITT vs control: 1.17 vs 1.23; P<.001), which persisted at 3-month follow-up (ITT vs control: 0.68 vs 0.91; P<.001). Both the ITT and PP groups exhibited greater improvements in self-efficacy (Cancer Behavior Inventory-Brief Version) than the control group at 1-month (ITT vs PP vs control: 82.83 vs 77.12 vs 65.35; P<.001) and 3-month intervention (ITT vs PP vs control: 92.83 vs 89.30 vs 85.65; P<.001). However, the change in social support (Social Support Rating Scale) did not increase significantly until 3-month intervention (ITT vs control: 50.09 vs 45.10; P=.002) (PP vs control: 49.78 vs 45.10; P<.001). All groups also experienced beneficial effects on quality of life (Functional Assessment of Cancer Therapy-Breast), which persisted at 3-month follow-up (P<.001). CONCLUSIONS: The intelligent mobile app AI-TA incorporating intelligent design shows promise for reducing psychological and cancer-related symptoms among young survivors of breast cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200058823; https://www.chictr.org.cn/showproj.html?proj=151195.

Prostate cancer with elevated free prostate-specific antigen density: A case report.

BACKGROUND: Prostate cancer is the second most common cancer among men worldwide, and prostate-specific antigen (PSA) is often used in clinical practice to screen for prostate cancer. Normal total PSA (tPSA) level initially excludes prostate cancer. Here, we report a case of prostate cancer with elevated free PSA density (fPSAD). CASE SUMMARY: A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy, and the postoperative pathological results showed acinar adenocarcinoma of the prostate. The patient is currently undergoing endocrine chemotherapy. CONCLUSION: We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

[Analysis of enzyme activity and substrate specificity of dolichyl-phosphate ß-glucosyltransferase].

Protein folding and quality control processes primarily occur in the endoplasmic reticulum (ER). ER-resident molecular chaperones play a crucial role in guiding nascent polypeptides towards their correct tertiary structures. Some of these chaperones specifically recognize glucosylated N-glycan moieties on peptide. It is of great significance to study the N-glycan biosynthetic pathway and glycoprotein quality control system by analyzing the sugar donor of ER luminal glucosyltransferases, known as dolichol phosphate glucose (Dol-P-Glc), or its analogues in vitro. In this study, we investigated a range of dolichol analogues to synthesize lipid phosphate glucose, which served as substrates for dolichyl-phosphate ß-glucosyltransferase E (Alg5E) derived from Trichomonas vaginalis. The results demonstrated that the recombinant Alg5E, expressed in Escherichia coli, exhibited strong catalytic activity and the ability to recognize lipid phosphate glucose with varying chain lengths. Interestingly, the enzyme's catalytic reaction was found to be faster with longer carbon chains in the substrate. Additionally, Alg5E showed a preference for branched chain methyl groups in the lipid structure. Furthermore, our study confirmed the importance of divalent metal ions in the binding of the crucial DXD motif, which is essential for the enzyme's catalytic function. These findings lay the groundwork for future research on glucosyltransferases Alg6, Alg8, and Alg10 in the synthesis pathway of dolichol-linked oligosaccharide (DLO).

Modulating the Microstructure and Surface Acidity of MnO2 by Doping-Induced Phase Transition for Simultaneous Removal of Toluene and NOx at Low Temperature.

It is a great challenge to remove VOCs and NOx simultaneously from flue gas in nonelectric industries. This study focuses on the construction of Fe-MnO2 catalysts that perform well in the simultaneous removal of toluene and NOx at low temperatures. Utilizing the Fe-induced phase transition of MnO2, Fe-MnO2-F&R catalysts with a composite morphology of nanoflowers and nanorods were successfully prepared that provided an abundant microporous structure to facilitate the diffusion of molecules of different sizes. Through in-depth investigation of the active sites and reaction mechanism, we discovered that Fe-induced phase transition could modulate the surface acidity of Fe-MnO2-F&R. The higher concentration of surface Mn4+ provided numerous Brønsted acid sites, which effectively promoted the activation of toluene to reactive intermediates, such as benzyl alcohol/benzoate/maleic acid. Simultaneously, Fe provided a large number of Lewis acid sites that anchor and activate NH3 species, thereby inhibiting NH3 nonselective oxidation. Furthermore, additional Brønsted acid sites were generated during the simultaneous reaction process, enhancing toluene activation. Consequently, the simultaneous removal of toluene and NOx was achieved through regulation of the physical structure and the concentration of acidic sites. The present work provides new insights into the rational design of bifunctional catalysts for the synergistic control of VOCs and NOx emissions.

Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice.

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.

[Advances in Mendelian randomization studies on autism spectrum disorder]. / å­Ÿå¾·å°”éšæœºåŒ–ç ”ç©¶åœ¨å­¤ç‹¬ç—‡è°±ç³»éšœç¢ä¸­çš„ç ”ç©¶è¿›å±•.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with onset in infancy or early childhood. Mendelian randomization (MR) is a statistical method used to infer causal relationships between exposures and outcomes. This article summarizes MR studies related to ASD. Existing research supports a causal relationship between maternal inflammatory bowel disease in children with ASD, parental education levels, screen time exposure, obesity, insomnia, serum transferrin, decreased blood selenium, abnormal signals in brain functional MRI, interleukin-6, phosphodiesterase 2A, mitogen-activated protein kinase kinase 3, mitochondrial ribosomal protein L33, serotonin, and ASD. However, it does not support a causal relationship between parental rheumatoid arthritis, systemic lupus erythematosus, neonatal jaundice in children with ASD, cytomegalovirus infection, asthma, oral ulcers, vitamin D levels, and ASD. This article reviews the etiological factors related to ASD and MR studies, aiming to explore and deepen the understanding of the pathophysiology of ASD. It provides strong statistical support for the prevention, diagnosis, and treatment of ASD, and offers new methods and strategies for the etiological analysis of complex traits.

LILRB2 inhibition enhances radiation sensitivity in non-small cell lung cancer by attenuating radiation-induced senescence.

Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.